Hematopoietic stem cell (HCT) transplantation offers curative therapy for a variety of malignant and non- malignant disorders. It is limited by donor availability, transplant related toxicity, graft vs. host disease (GVHD), malignant relapse, infections, and for some patients, reduction in their post-transplant quality of life. Continuing progress from the previous funding period, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) proposes to develop and execute scientifically meritorious, prospective clinical trials addressing key issues in HCT. Due to the complexity of pediatric transplantation, especially in those with rare inherited disorders, which are complex and difficult to study, we will devote special attention and focused scientific expertise to using the coordinated strength of the Network to improve BMT outcomes for this unique population. The BMT CTN will also amplify and leverage Network resources through collaborative research and ancillary studies of biologic endpoints that will be integrated with and complement clinical endpoints. The Network will also seek active collaboration with other scientific bodies including NCI- funded Cancer Cooperative Groups to improve the efficiency of clinical transplant studies for the large number of patients who could benefit from BMT and to maximize our successful completion of high quality and high priority clinical trials. The Fred Hutchinson Cancer Research Center is an ideal site to conduct multicenter Phase II and more importantly, prospective Phase III trials in six key areas including: alternative donors and graft sources;regimen related toxicity;GVHD;disease recurrence;infection and immune reconstitution;and late effects and quality of life. The Center is deeply committed to cooperative clinical research and can provide an outstanding environment in which to conduct the sorts of studies described with state-of-the-art clinical and laboratory facilities. RELEVANCE (See instructions): The major barriers to clinical studies in HSCT include the heterogeneity of conditions, the small numbers of individuals with an indication for HSCT at any one center, the differences in treatment strategies at various centers, and the lack of resources to coordinate national collaborative efforts. The Blood &Marrow Clinical Trial Network uses a multicenter approach to effectively conduct clinical trials of novel therapies in patients with uncommon conditions.